Objective: To investigate the distribution characteristics of Kidd blood group antigens, phenotypes and genotypes in Xinjiang and their influence on the risk of coronary heart disease. Methods: Samples from 7 981 patients treated at People's Hospital of Xinjiang Uygur Autonomous Region from August 1, 2023 to May 31, 2024 were collected for Jk(a-b-) phenotype screening via urea hemolysis test, followed by the third-generation sequencing (TGS). Kidd blood group Jk and Jk antigens in 1 081 patients with coronary heart disease and 1 021 healthy people were detected, and their phenotype frequency distribution was analyzed and corresponding gene frequencies were calculated. Correlation analysis and logistic regression were used to evaluate the influence of Kidd blood group antigen expression on coronary heart disease risk. Results: Two Jk(a-b-) phenotype samples were detected, both resulting from novel gene mutation combinations. Comparative analysis of two groups revealed a higher proportion of the Jk(a-b+) phenotype in the case group (22.5%, 243/1 081) than in the control group (18.5%, 189/1 021). Moreover, Kidd blood group phenotype distribution varied significantly across all ethnic groups in the case group (P<0.05). In the control group, the Hui ethnic group exhibited the highest JK JK genotype frequency 64.15% (34/53). In the case group, the highest JK allele frequency was observed in Mongol ethnic group 56.31% (125/222), and the lowest in Han patients 45.71% (341/746). The expression of Jk antigen was negatively correlated with coronary heart disease (P<0.05). Conclusion: The distribution of Kidd blood group system varied across ethnic groups in Xinjiang. The expression of Jk antigen may have protective effect on coronary heart disease, which provides a basis for future clinical blood transfusion treatment and the mechanism study of the correlation between Kidd blood group and coronary heart disease.

Objective To explore the difference in left ventricular reverse remodeling(LVRR)between coarctation of aorta(CoA)complicated by bicuspid aortic valve(BAV)and that by tricuspid aortic valve(TAV)after percutaneous intervention.Methods The clinical data on 47 patients undergoing percutaneous balloon dila-tion and stent implantation due to CoA in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2014 to December 2021 were retrospectively analyzed.According to the preoperative imaging data,there were 18 patients with BAVA and 29 with TAV.The results of echocardiography before and one year after the procedure were compared.Results CoA Vmax,CoA PG,LVEDd,LVEDdi,LVM and LVMI were significantly improved in CoA patients one year after percutaneous intervention,and 23.4%of the patients developed left ventricular reverse remodeling.AV Vmax,AV PG and LVEDdi in the patients with BAV were higher than those in the TAV group(P = 0.005 and P = 0.007;P = 0.03),and the rate of left ventricular reverse remodeling in BAV patients was lower than that in TAV patients,but there was no statistical significance.Multivariate analysis did not find any influence factors affecting left ventricular reverse remodeling one year after the procedure.Conclusions Part of the CoA patients develops left ventricular remodeling reversal one year after percutaneous intervention.LVRR in patients with BAV is lower than that in those with TAV,which still needs further clinical research.

Objective To compare and analyze the differences of clinical application of UpToDate by residents at home and abroad,and put forward some suggestions on the use of UpToDate in China.Methods On the basis of literature retrieval in Web of Science,CNKI and Wanfang database,the article summarized the present situations and advantages of UpToDate for residents at home and abroad,and compared the differences of clinical application research of UpToDate for residents at home and abroad by using Vosviewer.Results The application research of UpToDate for residents in foreign countries started earlier,and focused on the cognitive use,effectiveness evaluation,clinical teaching,suggestion updating,etc.,while the domestic researches started later and few studies focused on the theoretical research of UpToDate clinical teaching.Conclusion Drawing lessons from foreign experiences,we should increase the publicity and promotion of UpToDate in China,attach importance to its impact assessment,provide a feedback platform for professional clinical resources information,and actively change teaching methods by using UpToDate,so as to improve clinical decision-making ability.

Objective Based on the multi-software visual analysis of the literature on the effect of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway on rheumatoid arthritis in the past decade,the development trend and research hotspot in this field are summarized.To provide researchers with new directions and ideas to promote the innovative development of the field.Methods The literatures related to JAK/STAT signaling pathway in rheumatoid arthritis were collected from the Web of Science Core Collection database from 2013 to 2023.CiteSpace and VOSviewer software were used to analyze the number of publications,countries,authors and keywords of 354 articles retrieved.Results The number of published papers in this field continues to increase.According to the author's research direction,the presentation of high-frequency words,and the attention to the preface and hot topics,it is suggested that this field focuses on gene expression,immune mechanism,inflammatory mechanism,pathway inhibitors,drug therapy,etc.Future research will focus on the safety,mechanism and controlled trials of pathway inhibitors and antirheumatic drugs.Conclusion The effect of JAK/STAT signaling pathway on rheumatoid arthritis has attracted much attention in the past,present and future.There are differences in the research of different teams in this field,and the regional development is unbalanced,suggesting that we should strengthen cooperation and exchanges,focus on the international frontier,and carry out more high-quality research to promote the development and progress of this field,and provide clinical basis.

The codon sequence of the S1 protein of the SARS-CoV-2 Beta variant was optimized ac-cording to the preference of CHO cells and cloned into pSN expression vector to construct the re-combinant plasmid pSN-Beta-sl.Recombinant protein was expressed in CHO cells,identified using SDS-PAGE and Western blot,and purified through affinity chromatography.BALB/c mice were immunized with purified recombinant protein Beta-S1 combined with aluminum hydroxide adju-vant.Specific IgG antibody and its subtypes in serum and the cross-neutralization antibody activity against SARS-CoV-2 variants were evaluated.The results showed that the recombinant plasmid pSN-Beta-S1 was successfully constructed,and the recombinant protein Beta-S1 was produced u-sing the CHO cell expression system.The purified recombinant protein had a single band of about 120 kDa with the purity exceeding 85％and can bind to RBD pAb and strep-tag mAb.The recom-binant S1 protein showed good immunogenicity in BALB/c mice.The titers of specific IgG antibodies against RBD protein and S1 protein reached 1∶66 260 and 1∶133 120 on average 21 d after the third immunization,the antibody subtypes were mainly inclined to IgG1.Serum neutrali-zing antibody titer was 1∶629 for wild type,1∶1 720 for Beta,1∶374 for Delta,1∶77 for Omi-cron BA1 and 1∶101 for Omicron BA2.In this study,S1 recombinant protein of SARS-CoV-2 Beta variant was successfully expressed in CHO cell expression system and produced good immunoge-nicity and cross-neutralizing activity in BALB/c mice.These results provide a reference for the fur-ther development of broad-spectrum SARS-CoV-2 vaccine.

Objective:To explore the standardized performance of a FISH probe before clinical detection.Methods:The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test.Results:The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001.Conclusion:For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13⁺⁶ gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13⁺⁴ weeks (11⁺⁵ ~ 13⁺⁶ weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.
Pregnancy ; Humans ; Female ; Adult ; Infant ; Nuchal Translucency Measurement/methods* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Aneuploidy ; Fetus/diagnostic imaging* ; Ultrasonography, Prenatal ; DNA Copy Number Variations ; Transcription Factors

Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

Objective:To investigate the relationship between the expression level of thymocyte selection-associated high mobility group box protein ( TOX) gene and the radiosensitivity of lower-grade glioma (LGG) patients. Methods:Using bioinformatics research methods, 474 LGG patients from The Cancer Genome Atlas (TCGA) database were selected as the test set (TCGA-474 set), and two different genetic data sets ( n=412 and n=171) from the Chinese Glioma Genome Atlas (CGGA) database were selected as the validation set (CGGA-412 set and CGGA-171 set). Patients were stratified based on whether received radiotherapy, and divided into the high and low TOX expression group according to the expression level of TOX gene in LGG. Survival curves of all patients were plotted. The overall survival (OS) and progression-free survival (PFS) of patients in the high and low TOX expression groups were compared and analyzed using log-rank test. Results:Multivariate analysis of OS in the TCGA-474 set showed that high expression of TOX was a protective factor for OS ( HR=0.061, 95% CI: 0.005-0.791, P=0.044). After stratification analysis based on radiotherapy and adjustment for confounding factors, the HR (95% CI) of patients with high TOX expression in the TCGA-474, CGGA-412, and CGGA-171 sets were 0.405 (0.261-0.629), 0.581 (0.418-0.806), and 0.464 (0.269-0.800), respectively, with P values of <0.001, 0.001, and 0.008, respectively. Among patients receiving radiotherapy in the TCGA-474 set, the OS and PFS of patients with high TOX expression were significantly longer than those in the low TOX expression group, and the differences were statistically significant (both P<0.001). The OS benefit of patients with high expression of TOX was significantly prolonged in both the CGGA-412 and CGGA-171 sets compared to those with low TOX expression, and the differences were statistically significant (both P<0.001). Conclusion:The high expression of TOX may be related to the radiosensitivity of LGG, which may be a gene marker of the radiosensitivity of LGG.

Objective:To establish and validate analytic performance of laboratory-developed real-time quantitative polymerase chain reaction (RQ-PCR) test (LDT) for BCR::ABL1 p210 transcript.Methods:Using the primes and probes released by the Europe Against Cancer Program(EAC), we have established BCR::ABL1 p210 RQ-PCR test. The laboratory-specific conversion factor (CF) was determined by the WHO 1 st International Genetic Reference Panel, and a two-level internal control is developed using a mixture of K562 and HL60 cell lines was created to ensure traceability. Analytical performance, including analytical accuracy, analytical precision, linearity range, analytic sensitivity and specificity of RQ-PCR LDT test for BCR::ABL1 p210 transcript were validated according to CLIS guidelines. Furthermore, a comparison was made with an FDA-cleared RQ-PCR in vitro diagnostics (IVD) kit by Bland-Altman analysis. Results:The laboratory specific conversion factor (CF) for LDT RQ-PCR was determined to be 0.535 based on WHO 1 st International Genetic Reference Panel, which can be used to convert to the BCR::ABL international scale (BCR::ABL1 IS) reliably. The repeatability of BCR::ABL1 IS results at 4 different molecular response (MR0.5,MR1.5,MR2.5,MR3.5) levels are 7.44%, 5.33%, 9.12% and 18.06%, respectively, with total precision of 7.99%, 5.49%, 10.95% and 17.99%. The previous CAP proficiency test (PT) results from our laboratory were within the acceptable range of variation. MR results of our laboratory and MR mean value of all CAP-PT laboratory is highly correlated ( r=0.999, P<0.01), and consistent according to Bland-Altman analysis. Furthermore, the LDT method in our laboratory has a high correlation with the test results of FDA-cleared Qiagen IVD kit ( r=0.997, P<0.01). BCR::ABL1 IS results of BCR::ABL1 e13a2 transcript showed linearity within the range of 0.001%-7.454%, with a maximum coefficient of variation (% CV) 64.09%. The linearity range of e14a2 transcript BCR::ABL1 IS was 0.002%-12.398%, with a maximum % CV of 43.37%. The test has a limit of detection (LoD) of MR5.0 (0.001% IS) for e13a2 and MR4.8 (0.002% IS) for e14a2 transcript, respectively. The limit of quantitation (LoQ) for both e13a2 and e14a2 transcripts was MR4.7 (0.002% IS). The test exhibited 100% specificity, with no cross-reactivity observed between the p190 transcript and p210. Conclusions:The analytic performance of BCR::ABL1 p210 LDT RQ-PCR test from our laboratory is excellent, which can meet the clinical needs of BCR::ABL1 detection in patients with chronic myeloid leukemia.